High intensity focused ultrasound (HIFU) therapy has emerged as a truly non-invasive medical procedure for solid tumor treatment. However, the volume of the lesion following a single HIFU sonication is small. As a result, it can take up to several hours to ablate a relatively small tumor. In addition, highly vascularized (perfused) tissues are more resistant to thermal ablation than poorly perfused areas owing to the cooling effect of blood circulation. Therefore, a prolonged heating duration will be required in highly vascularized tissues. Skin burns, which are usually limited to subcentimetre superficial burns, are also often observed after HIFU treatments because ultrasonic energy deposition reaches a local maximal at skin surface. To facilitate HIFU process and avoid or minimize skin burns, we need to enhance HIFU-induced heating in the targeted tissue at a relatively low ultrasound intensity level. The effectiveness of HIFU-induced heating is related to the local ultrasound absorption. The increase of ultrasound absorption in the targeted tissue can effectively improve the heating outcome of HIFU treatment. The injection of ultrasound contrast agents or nanoparticles into the targeted tissue has been studied as a method to increase the local ultrasound absorption and enhance HIFU heating. In the current project, we propose to evaluate a photo-enhanced particle-free technique to facilitate HIFU ablation. Our central hypothesis is that HIFU therapy can be improved by a diagnostic laser system without the injection of any micro-, or nano-particles into the body. We have two specific aims: 1) investigate and optimize photo- enhanced particle-free HIFU heating: ex vivo study; and 2) evaluate photo-enhanced particle-free HIFU heating in a rodent model. We believe that the success of the proposed research will lead to an enhanced HIFU therapy for solid tumor treatments, which include the treatment of breast tumors, prostate tumors, head and neck cancer.